Bone tumors represents the major cause of morbidity and mortality associated with many types of cancer. Currently, the conventional procedure for treatment of bone tumor involves a combination of surgical resection, radiation and/or chemotherapy. Despite recent advances in the management of neoplastic diseases, the prognosis and quality of life for patients with aggressive bone tumors undergoing such multimodal therapies is still poor. Current experimental approaches for treatment of tumors are focused on the localized delivery of inhibitors of growth and neovascularization.
Collagens and glycosaminoglycans are two classes of biomaterials suited for use in bone regeneration. Collagen based matrices have been used in bone grafting. Type I collagen has good cell adhesive properties, in particular, for bone forming osteoblast cells.
Hyaluronic acid is a natural component of the extracellular matrix in many tissues including bone, and it is readily sterilized, is biodegradable and can be produced in a wide range of consistencies and formats. It is generally biocompatable and its resorption characteristics can be controlled by the manipulation of monomers to polymer forms, most commonly through the esterification of the carboxylic groups of the glucuronic acid residues.
The TGF-.beta. superfamily consists of a large group of growth factors that exert profound influences on cellular morphology and the growth and differentiation of many cell types both in vitro and in vivo. The members of this superfamily are distinguished from other growth factors based on their unique ability to induce cell cycle arrest and the differentiation of mesenchymal cells and uncommitted cells during embryogenesis (Massague, J. S., Cheifetz, F. T., Andres, J. L. Ann. NY. Acad. Sci. 593:59-72, 1990). The mechanism of TGF-.beta. induced cell cycle arrest is among the most intensively studied over the last decade. Members of this family include TGF-.beta.1, .beta.2 and .beta.3, the Bone Morphogenetic Proteins (BMPs), and growth and differentiation factors (GDFs).